Since its introduction in the early 1990's, optical coherence tomography (OCT) has strongly impacted ophthalmic diagnostics through its ability to image retinal pathologies noninvasively with micron-scale resolution. Recent demonstrations of OCT imaging in the anterior segment indicate that this technology may also soon find routine applications in diagnosis of corneal pathologies, glaucoma, and in refractive surgery. 2 new optical technologies have recently been introduced which are poised to revolutionize ophthalmic OCT yet again, however each currently suffer from technical limitations which limit their potential applicability. The recent introduction of spectral domain OCT (SDOCT) for retinal imaging has dramatically altered the landscape by allowing for ~100x faster image acquisition rates than the conventional time-domain approach. Importantly, this advance allows for rapid accumulation of volumetric macular datasets, in which individual cross-sectional images are readily correlated with their exact macular position and pathologies may be characterized in 3 dimensions. However, current implementations of SDOCT suffer from fundamental technical limitations which limit the available imaging depth to ~2mm, with significant fall-off of image signal-to-noise ratio as a function of depth below ~1mm. Thus, this exciting new capability is not well suited for imaging vitreous abnormalities, deep retinal/choroidal pathologies, optic nerve head morphology, or any structures deeper than the cornea in the anterior segment. A second optical innovation which could dramatically impact ophthalmic diagnostics is the recent introduction of molecular contrast imaging in OCT. IGG angiography is a fundamental diagnostic technique in ophthalmology, but its fluorescence is not detectable in OCT because of the inherent insensitivity of OCT to incoherent scattering processes. In this exploratory/developmental project, we will implement new technology to address both of these limitations. The specific aims of the project are to: 1. Extend the available imaging depth of spectral domain optical coherence tomography (SDOCT) for both retinal and anterior segment imaging applications by implementing a novel spectrally structured illumination approach; 2.Apply new concepts in molecular contrast optical coherence tomography (MCOCT) to allow for real-time, three-dimensional (3D)imaging of ICG infiltration of the retinal and choroidal vascular networks; and 3.Demonstrate both new techniques in living patients through close collaboration between engineering and clinical co-investigators. [unreadable] [unreadable] [unreadable]